Tissue expander inflating due to osmotic driving forces of a shaped body of hydrogel and an aqueous solution

ABSTRACT

A self-inflating tissue expander (1) serves to create cavities for the insertion of implants or to provide tissue for a self transplantation. The tissue expander itself is implanted into the tissue, where it absorbs body fluid, especially water from the surrounding tissue due to an osmotic driving force. The tissue expander (1) has a shaped body (5) made from hydrogel (2).

FIELD OF THE INVENTION

The invention relates to a self-inflating tissue expander to createcavities for the insertion of implants or to provide tissue for a selftransplantation, where the tissue expander itself is implanted in thetissue and where it absorbs body fluid, especially water from thesurrounding tissue due to an osmotic driving force. In order to createcavities for the insertion of implants, but also to provide healthytissue for a self transplantation, the method of controlled tissueexpansion is applied. The tissue is continually stretched under amoderate application of pressure until the desired cavity or the desiredamount of additional tissue is obtained.

BACKGROUND OF THE INVENTION

From the dissertation "Controlled Tissue-Expansion in ReconstructiveSurgery" (Julian H. A. van Rappard, Thesis Groningen, The Netherlands,1988) a tissue expander is known that is expanded by the gradual fillingwith a liquid. The tissue expander has an impermeable, stretch-resistantskin and a self-sealing valve for the filling with liquid using a hollowneedle and a syringe. The tissue expander is implanted under the tissueto be expanded, with the valve arranged so that it is accessible by theneedle from the outside. For the actual expansion of the tissue, thetissue expander is gradually filled with liquid. The needle is insertedinto the valve through the tissue and the liquid is injected into thetissue expander with the syringe. When fully filled with liquid, thetissue expander obtains a shape determined by the form of its skin. Theforming of the skin is adaptable to various applications in this way. Itis an advantageous feature of the known tissue expander that a preciselycontrolled expansion of the tissue is possible. A major disadvantage,though, is the occurrence of high peak pressures after each filling ofliquid into the tissue expander. This concerns especially the regions oftissue to be expanded located directly next to the tissue expander.These regions are compressed so much that damage of the tissue occurrs.When reducing the amount of liquid that is injected into the tissueexpander in each step, problems result from the frequent piercing of thetissue in the region of the valve. Furthermore, the valve may develop aleak, which renders the tissue expander useless. There is no danger forthe tissue surrounding the tissue expander as a result of a leaky valve,as long as a physiologically safe, sterile liquid for the filling of thetissue expander.

A self-inflating tissue expander of the type described above is knownfrom the article "A Self-Inflating Tissue Expander" (E. D. Austad etal., Plastic and Reconstructive Surgery, Vol. 70 No. 5, pages 588 ff).This tissue expander consists of a silicone membrane filled with asodium chloride solution. The molarity of the sodium chloride solutionis greater than the physiological molarity of approximately 0.3. Theosmotic driving force, which drives body liquid from the tissuesurrounding the tissue expander through the semipermeable siliconemembrane into the tissue expander, is based on this. The inflation ofthe tissue expander, and therefore also of the tissue surrounding thetissue expander, occurrs without the need of any manipulations from theoutside. Furthermore, the tissue surrounding the tissue expander has anexceptional, undamaged quality after the expansion. The reason for thisis that the self-inflating tissue expander does not create pressurepeaks on the one hand, and that the intake of body fluid into theexpander stimulates the metabolism of the surrounding tissue on theother hand. A disadvantage is the small amount of volume expansion ofthe tissue expander, at least as long as the molarity of the sodiumchloride solution initially does not exceed a physiologically acceptablevalue by far. Another disadvantage is that the properties of thesilicone membrane change with the expansion. Especially the pore size ofthe silicone membrane steadily increases. In this way an increasingamount of sodium chloride ions can pass through the silicone membrane.This leads to a decrease in the osmotic driving force, though, which isnot coupled with a gain in the volume expansion of the tissue expander.A further disadvantage of the known tissue expander is the lack of apossibility to influence the direction in which the expansion of thetissue takes place. The form of the silicone membrane has only a minorinfluence on the shape of the tissue expander after its inflation. It isfurthermore established that the inflation of the silicone membraneitself uses up a considerable amount of the osmotic driving force of thetissue expander. This is compounded by the fact that the stretching ofthe silicone membrane needs more strength as the volume of the tissueexpander increases, while the osmotic driving force decreases at thesame time. Only a strongly decreasing resulting driving force is thenleft for the expansion of the tissue surrounding the tissue expander,and the ratio of the initial size of the tissue expander to theattainable final size is further reduced beyond the calculated value.

From the U.S. Pat. No. 4,237,893 a device to widen the cervix is known.The device has a rod-shaped outer form and an at least three layeredinterior structure. An intermediate layer is made from a hydrophilicpolymer material, i. e. a hydrogel. The device is introduced into thecervix and there expands by taking up body fluid from the uterus. Bythis the cervix is widened in its cross section. When the desiredopening of the cervix has taken place after some hours the device isremoved and a surgery can be performed through the cervix. The knowndevice serves to temporarily widen an existing orifice of the body, butneither is a new orifice created, nor is additional tissue created.Furthermore, the known device to widen the cervix is not meant to beimplanted in the tissue, but to be introduced into an already existing,open body orifice.

The U.S. Pat. No. 3,867,329 describes a method for making a rod-shapedbody from hydrogel, which is supposed to serve as a device to widen thecervix. At first a copolymerisation of different aqueous substances iscarried out and the resulting copolymer is then further treated. Theresulting hydrogels have a swelling coefficient of up to 25 after 5 daysin distilled water. Information about a swelling coefficient in aphysiological sodium chloride solution is not contained in the U.S.Patent.

From the U.S. Pat. No. 3,975,350 it is known to use a hydrogel made froma polyurethane polymer as an implantable carrier of drugs. The aspect oftissue expansion is not mentioned in the U.S. Patent.

It is known to make so called soft contact lenses from hydrogel. Underthe generic term hydrogel polymer substances are understood, whichexpand in an aqueous environment by taking up water. The amount ofexpansion is very different, depending on the hydrogel. It is quantifiedby the swelling coefficient. A swelling coefficient of n means that theinitial volume has increased n-fold by taking up water. A constituent ofthe swelling coefficient is the naming of the solution in which it wasdetermined. It is immediately seen that due to the higher osmoticpressure the swelling coefficient in distilled water will always belarger than in e. g. a physiological sodium chloride solution. Thehydrogel from which soft contact lenses are made has a swellingcoefficient of less than 4 in a physiological sodium chloride solution.It also has an advantageously high form stability and tear resistance inthe swollen state.

SUMMARY OF THE INVENTION

The soft contact lenses "Geaflex 70" from the company "wo/hlk-contact-linsen" consist of a copolymer of methylmethacrylate (MMA)and vinylpyrrolidone (VP). It is a solvent-free cross-linked, non-ioniccopolymer with free methylene side chains.

It is the object of the invention to provide a self-inflating tissueexpander, which in particular allows a directionally controlledexpansion of the surrounding tissue on a large scale.

According to the invention this is realised by providing a shaped bodyof hydrogel. In the simplest embodiment the tissue expander consistsexclusively of a shaped body of hydrogel. It is understood that only ahydrogel that retains its shape or at least does not dissolve whentaking up water is to be used. Otherwise the removal after the expansionof the tissue would be difficult. A hydrogel that is suitable for theproduction of the shaped body is the hydrogel from which the known softcontact lenses are made.

An improved swelling capability is obtained when the hydrogel is anionic hydrogel. The osmolarity of the hydrogel is increased by theion-anion-dissociation of the hydrogel in aqueous solution.

Especially well suited as constituents of tissue expanders are ionichydrogels that are formed on the basis of a fully cross-linked,non-ionic polymer. In this way the ionic hydrogel has the mechanicalstability of a non-ionic polymer, but at the same time a significantlyhigher swelling coefficient as compared to non-ionic hydrogels. An ionichydrogel is obtained in a comparatively easy way when a non-ionichydrogel is saponified.

The saponifiable non-ionic hydrogel may be a polymer on the basis ofmethylmethacrylate (MMA). Such polymers have methylene side chains thatare transformed into carboxyl side chains under the influence of sodalye and under the separation of methylene. In an aqueous solution thecarboxyl groups dissociate into negatively charged CO₂ ⁻ -groups andfree H⁺ -ions.

The shaped body may be surrounded by a selectively permeable membrane.In this way hydrogels can be used that grow to 20 times their initialvolume taking up water in physiological solutions. The accompanyingdissolving of the hydrogel happens only inside the selectively permeablemembrane. It is understood that the selectively permeable membraneshould essentially be permeable for water. For this reasonsemi-permeable membranes are suited for the tissue expander. But alsoselectively permeable membranes which next to water are permeable forsmall ions may advantageously be applied. In any case lies the cut-offlimit of the selectively permeable membrane below approximately 4micrometers, so that blood cells are effectively held back.

The selectively permeable membrane may be stretch resistant. By this theshape of the inflated tissue expander may be predetermined by the designof the membrane.

It is of advantage to pre-wet the membrane. It is necessary to conditionthe selectively permeable membrane prior to the application of thetissue expander, so that sufficient permeation rates are obtained fromthe beginning on. When the conditioning is performed by the tissuesurrounding the tissue expander a lot of time is lost. So it is sensibleto bring the membrane to a moisture level that ensures the desiredfunction before the implantation of the tissue expander.

An aqueous solution may be provided inside the membrane. The aqueoussolution ensures that all surfaces of the shaped body are wetted andtherefore available for the taking up of water and the expansion of thehydrogel.

Sodium chloride or some other physiologically tolerated salt may bedissolved in the solution. The salt helps to create a further osmoticdriving force which acts between the tissue surrounding the tissueexpander and the solution. This force itself also leads to an expansionof the tissue expander, but mainly serves to provide a sufficient amountof water for the expansion of the hydrogel. Furthermore, the salt can beused to specifically exploit certain properties of some hydrogels. Thesehydrogels can take up water only when the concentration of salt in theirvicinity does not exceed a certain value. Conversely they ensure bytaking up water that the concentration of salt in their vicinity doesnot fall below a certain value. By this the osmotic driving forcebetween the tissue surrounding the tissue expander and the solution isalways maintained so far that water enters the tissue expander, by whichthe hydrogel itself ultimately ensures its supply with water.

Instead of or additionally to the salt, macromolecules with especiallypolyelectrolytic properties may be dissolved in the solution.Macromolecules such as protein or carbohydrate molecules even cannotpass through selectively permeable membranes that have high permeationrates for water and are transmissiable for sodium chloride ions. Byvirtue of this property they are permanently available to keep up theosmotic driving force. Polyelectrolytic properties of the macromoleculessupport the purely osmotic driving force by additional electrochemicaleffects.

The solution may be approximately unimolar. This value refers to theinitial concentration of the solution. It ensures that the volumeoccupied by the solution at time of the implantation of the tissueexpander is small at first, but that the wetting of the shaped body isensured even after its swelling. A unimolar sodium chloride solution isnot physiologically tolerable, as a skilled person will immediately see.The molarity of one should therefore be attained through the use ofdifferent dissolved substances, especially proteins.

The shaped body of hydrogel may be separated into a number of individualbodies. The time it takes for the hydrogel to obtain its maximumexpansion is primarily determined by the dimensions of the shaped body.This means that the speed of the expansion of the shaped body may beaccelerated by the separation into individual bodies. On the one handthe distance the water has to go through the hydrogel is limited and onthe other hand a larger surface area for the entry of the water into thehydrogel is provided.

A gas-filled pressure buffer may be provided in the tissue expander.Gas-filled pressure buffers are extremely well suited to neutralizepressure peaks. Actually, pressure peaks do not occur with the newtissue expander as opposed to non self-inflating tissue expanders, butthe pressure exerted by the tissue expander on the surrounding tissuemay be distributed more evenly by the insertion of the pressure buffer.Carbon dioxide is especially suited as a filling gas, since it isresorbed by the surrounding tissue when released. The pressure buffermay be arranged at any place inside the tissue expander, e. g. insidethe shaped body of hydrogel or next to the shaped body in the membraneenclosing the shaped body.

The shaped body or the individual bodies of hydrogel and/or the membranemay be partially vapour-coated with a metal, especially a noble metal.By the partial vapour-coating with metal the active surface area of theshaped body or the individual bodies is reduced. This also reduces theirswelling speed. This is sensible when, for instance, an especially slowexpansion of tissue by the tissue expander is to be attained.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is further explained and described with the aid of twopreferred embodiments. The Figures show:

FIG. 1 illustrates a first embodiment of the self-inflating tissueexpander,

FIG. 2 illustrates a second embodiment of the self-inflating tissueexpander,

FIG. 3 illustrates a structural formula of the tissue expander accordingto FIG. 1, and

FIG. 4 illustrates a structural formula of a further embodiment of thetissue expander.

DETAILED DESCRIPTION

The approximately rod-shaped tissue expander 1 shown in FIG. 1 isintended for the expansion of the periosteum. More specifically it isintended for the expansion of the periosteum of the upper side of ajawbone crest, until enough material to form new bone matter to build upa raised jawbone crest can be brought into the pocket in the periosteumthus created. The raising of the jawbone crest often is a prerequisitefor the sensible employment of tooth prostheses with patients that havebeen without teeth for a long time. The tissue expander 1 consistsexclusively of a shaped body 5 made of hydrogel 2. The hydrogel is rigidin a dry state before the implantation, so that it may easily beinserted into a pocket between the jawbone crest and the liftedperiosteum. The hydrogel 2 is based on a copolymer of methylmethacrylate(MMA) and vinyl pyrrolidone (VP). The hydrogel 2 further containsadditives, with which a good mechanical and form stability of the tissueexpander is obtained. The hydrogel 2 is of identical composition as thehydrogel used for the manufacturing of the soft contact lenses "Geaflex70" by the company "wo/ hlk-contact-linsen". The physiologicaltolerability of this hydrogel has been proven to a large degree. In aphysiological sodium chloride solution the hydrogel swells by taking upwater until 3.6 times the initial volume is obtained. For thisapproximately 220% of the starting weight of the hydrogel is absorbed inthe form of water. The driving force of this taking up of water is ofosmotic nature, with the surface of the hydrogel acting as a membrane.The tissue expander 1 reaches a similar degree of swelling insurrounding human tissue as does the hydrogel 1 in a physiologicalsodium chloride solution, since all human body fluids are in a quiteprecise osmotic equilibrium with a physiological sodium chloridesolution. Reductions have to be taken into consideration for theresistance the expanding tissue, in this case the periosteum, putsagainst its stretching by the tissue expander 1. In the case of theexpansion of periosteum a swelling by a factor of three with respect tothe initial volume in the tissue is sufficient, though. It is especiallyadvantageous that the shaped body 5 of the tissue expander 1 even in theswollen state remains a single, tear resistant piece of hydrogel andthat is does not show any signs of deterioration. This makes theexplantation of the tissue expander much easier. After the explantationit is to be noted that the periosteum expanded by the tissue expanderhas a very good constitution, since it was exposed to a constantmetabolism just by the taking up of water by the tissue expander. Thebone forming matter put under the periosteum to build up the jawbonecrest are thus converted to bone substance more quickly.

In some cases the degree of expansion by a factor of three with respectto the initial volume, which can be obtained with the tissue expanderaccording to FIG. 1, is not sufficient. For these cases the tissueexpander 1 according to FIG. 2 is provided. Here the tissue expander 1has a shaped body 5 of hydrogel 2 inside of a closed membrane 3. Thecomposition of the hydrogel is chosen so that it loses its formstability and also its mechanical stability in the swollen state, butthat it reaches a final volume up to 20 times the initial volume. Theexplantability of the tissue expander 1 according to FIG. 2 therefore isbased on the membrane 3 surrounding the hydrogel 2. The membrane 3 isformed to be selectively permeable and allows an unhindered passage ofwater from the tissue surrounding the tissue expander 1 to the hydrogel2, while it is impenetrable for larger molecules. The "NADIR"-membranesof the company "Hoechst AG", for instance, which are based on cellulose,cellulose acetate or polyamide, and which are stabilized by acomparatively large pored support membrane made of polypropylene, aresuitable as material for the membrane 3. The design of the membrane 3determines the shape of the tissue expander 1 after its inflation. Themembrane 3 has to be conditioned, i. e. wetted, before the tissueexpander 1 is implanted, so that it has a high rate of permeation forwater from the surrounding tissue from the beginning on. In order toensure the taking up of water by the hydrogel 2 from the beginning, anaqueous solution 4 is provided inside the tissue expander 1 alreadybefore the implantation. The solution 4 is in contact with the insidesurface of the membrane 3 and fully wets the surface of the tissueexpander 1. It serves as a mediator between the hydrogel 2 and themembrane 3 or the tissue surrounding the tissue expander 1. The solution4 itself should have an osmotically acting concentration with respect tothe surrounding tissue. This ensures that the volume of the solution 4increases, so that the hydrogel 2 is fully wetted by the solution 4,even when swollen to a high degree. Sodium chloride or alsophysiologically tolerable macromolecules are suitable as additives tothe solution 4. The latter are retained especially easily in the tissueexpander by membranes which have very high permeation rates for waterand therefore also let sodium chloride pass in a certain amount. Thetissue expander presented here is suited, for instance, to create acavity for a silicone implant to construct an artificial breast.

Apart from the fashioning of the tissue expander according to FIG. 2there is a further possibility to increase the swelling cofficient ofthe tissue expander of hydrogel according to FIG. 1. This possibility isexplained with the aid of FIGS. 3 and 4, where FIG. 3 is the structureformula of the hydrogel 2 of the shaped body 5 according to FIG. 1 andFIG. 4 is the structure formula of a further, not separately shownshaped body of a further embodiment of the tissue expander. As describedabove, the hydrogel 2 of the shaped body 5 according to FIG. 1 is acopolymer of methylmethacrylate (MMA) 6 and vinyl pyrrolidone (VP) 7.The structure has free methylene side chains 8, as shown in FIG. 3. Whenthe structure is saponified with soda lye according to FIG. 3, thestructure according to FIG. 4 is produced by the separation ofmethylene. Here there is a free carboxyl group 9 in the vicinity of themethacryl group 6' instead of the methyl group 8. The carboxyl groupdissociates in an aqueous solution into a negatively charged rest CO₂ ⁻and a free ion H⁺ . In this way the osmolarity of the hydrogel 2 isincreased by saponifying. A hydrogel with the structure formulaaccording to FIG. 4 has a swelling coefficient of more than 30 indistilled water and of approximately 10 to 12 in a physiological sodiumchloride solution. Even so, the mechanical stability after thesaturation of the hydrogel with water is still good. The reason for thisis that the basic structure responsible for the mechanical propertieshas not been changed by the saponification.

In the following a method is described, with which the copolymer ofmethylmethacrylate (MMA) and vinyl pyrrolidone (VP) of the tissueexpander according to FIG. 1 has been successfully treated, in order tosignificantly improve its swelling properties. The following numbersrefer to compact pieces of polymer approximately 1 cm³ in size. Thestated times are to be increased for larger pieces of polymer due to thelonger diffusion times and they are to be decreased for smaller piecesor pieces with a large relative surface area. At first the copolymer issaponified with a unimolar soda lye for five days. It is then washed indistilled water, which is renewed a number of times, for 30 days, inorder to remove rests of the soda lye from the copolymer. Already afterthe saponification does the copolymer have the structure shown in FIG.4. After the washing the copolymer is brought into equilibrium in sodiumchloride solutions with ascending concentrations. This causes an osmoticshrinking of the copolymer previously saturated with distilled water.Suitable are concentrations of the sodium chloride solution beginningwith 0.1%, ascending over 0.3% and 0.5% to 0.9%. This bringing into anequilibrium is done in the respective solution for a duration of 1 to 3days. The final value of the concentration of the sodium chloridesolution of 0.9% corresponds to a physiological sodium chloridesolution. The not fully dehydrated copolymer is put into a germ proofbut steam transmitting enclosure and sterilized therein for 10 minutesat 120° C. in an autoclave. Finally there is a curing at roomtemperature and reduced humudity, in order to reduce the water contentof the copolymer so far that it is nearly water free. The copolymerremoved from the germ proof enclosure has a swelling coefficient of 12in a physiological sodium chloride solution.

In a variation of the prescribed method the copolymer is additionallybrought into equilibrium with a sodium chloride solution which has aconcentration that is higher than that of a physiological solution andwhich e.g. has a concentration of 1.2%. This causes a higher degree ofsaturation of the carboxyl groups 9 of the copolymer ionized bydissociation, with the aid of Na⁺ -ions dissociated in the sodiumchloride solution. This results in quasi-non-ionic properties; of thedehydrated hydrogel during the renewed taking up of water, until the Na⁺-ions have diffused out of the copolymer. The initial reduction in theswelling speed accompanying this is advantageous, since it especiallyprevents excessive strain of the tissue surrounding the tissue expanderafter the implantation.

While the foregoing specification and drawings disclose preferredembodiments of the invention, it will be understood by those skilled inthe art that variations and modifications thereof can be made withoutdeparting from the spirit and scope of the invention as set forth in thefollowing claims.

I claim:
 1. A tissue expander for creating cavities for the insertion ofimplants or to provide tissue for a self transplantation comprising ahydrogel having a shaped body with a surface, said surface acting as amembrane disposed therearound, said hydrogel being capable of inflatingdue to an osmotic driving force of said hydrogel, a second selectivelypermeable membrane disposed around said first mentioned membrane anddefining a space therebetween, and an aqueous solution disposed in saidspace between said membranes and generating an osmotic driving force forinflating the tissue expander.
 2. A tissue expander as defined in claim1, wherein said hydrogel is an ionic hydrogel.
 3. A tissue expander asdefined in claim 1, wherein said hydrogel is a saponified non-ionichydrogel.
 4. A tissue expander as defined in claim 1, wherein saidhydrogel is non-ionic and is a polymer on the basis ofmethylmethacrylate (MMA).
 5. A tissue expander as defined in claim 1, inwhich said aqueous solution has a molarity of approximately
 1. 6. Atissue expander as defined in claim 1, in which sodium chloride, anotherphysiologically tolerated salt, or a macromolecule with polyelectrolyticproperties is dissolved in said solution.